Extract

Anecdotal, Historical and Critical Commentaries on Genetics

Edited by Adam Wilkins

ERNST Caspari was the first researcher to use methods of developmental biology to analyze the action of a gene. By transplanting larval tissue between the wild type and a red-eyed mutant of the moth, Ephestia, he demonstrated that wild-type larvae produce a diffusible “substance” that is lacking in the mutant and is necessary for the development of eye pigmentation. Further characterization of the substance and an approach to isolate it were interrupted by the Nazi government dismissing Caspari according to the Nuremberg anti-Semitic laws. He escaped to Turkey and later to the United States but did not get a chance to further contribute to the rapid development in the field, which led to the “one-gene-one-enzyme” hypothesis. Caspari's results, published in 1933, represent the first step toward this hypothesis of gene action.

Seventy-five years ago, the young geneticist Ernst Caspari published some experiments that provided novel insight into a hitherto unsolved basic problem of genetics: How do genes function to produce characters? Both the physical nature of genes and the mechanisms of their action were completely unknown at that time, but were of course the subject of intense speculation. In developmental biology, genetic concepts and methods played no role. In the beginning of the century, Theodor Boveri had performed experiments on the development of the nematode worm, Ascaris, in which he demonstrated that the mode of chromosome distribution in early cleavage was under cytoplasmic control. Somatic nuclei in Ascaris lose considerable numbers of fragments of their chromosomes during the first cleavage mitotic divisions, whereas germ-line nuclei retain the entire genome. This developmental program, Boveri found, depended on the cytoplasmic environment, as experimental relocalizations of the cleavage planes and alterations in the number of blastomeres derived from the animal and the vegetal half of the egg, respectively, yielded corresponding alterations in the numbers of germ-line and somatic blastomeres. These experiments led Boveri to conclude that the developmental fates of the blastomeres were due to extremely small differences within the egg cytoplasm that lead to differences between descendant cells “by repeatedly triggering changes in the nuclei that act back on the cytoplasm” (Boveri 1910, p. 191; I have translated several quotations from German). But even 20 years later, interactions between nucleus and cytoplasm had no place in Spemann's organizer concept (Spemann 1936), which instead led to laborious efforts in many laboratories to isolate animalizing and vegetalizing factors. Spemann as well as other developmental biologists of the time never considered genetic influences in development, and many decades were to pass until genetic methods were applied to identify the molecular basis of organizer action (e.g., Cho  et al. 1991).

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